Impact of Chronic Stress and Anxiety on Interleukin-6, Hypoxia-Inducible Factor-1α and on Pathological and Immunohistochemical Parameters in Breast Cancer

Yahia, Saddek; Tahari, Zineb; Medjdoub, Asmahame; Bessaih, Nadia; Messatfa, Moussa; Lahmer, Miloud; Seddiki, Sonia; Sahraoui, Tewfik

doi:10.31557/APJCP.2025.26.9.3271

Impact of Chronic Stress and Anxiety on Interleukin-6, Hypoxia-Inducible Factor-1α and on Pathological and Immunohistochemical Parameters in Breast Cancer

Document Type : Research Articles

Authors

¹ Biology of Development and Differentiation Laboratory, Ahmed Ben Bella Oran, University, Oran, Algeria.

² Department of the Living and Environment, University of Sciences and Technology of Oran, Mohamed-Boudiaf, Oran, Algeria.

³ Department of Medical Oncology, University Hospital Establishment of Oran, Faculty of Medicine, Ahmed Ben Bella Oran 1 University, Oran, Algeria.

⁴ Faculty of Medicine, Abdelhami Ibn Badis University Mostaganem, Mostaganem, Algeria.

⁵ Immunology Laboratory, Pasteur Institute of Oran, Oran, Algeria.

⁶ The National Center of Research in Social and Cultural Anthropology, Oran, Algeria.

10.31557/APJCP.2025.26.9.3271

Abstract

Objective: The Aim of this study is to evaluate stress and anxiety by rating scale in breast cancer (BC) patients and their association with interleukin-6 (IL-6), hypoxia-inducible factor-1α (HIF-1α), pathological and immunohistochemical parameters. Methods: We analyzed serum concentrations of IL-6 and HIF-1α in 69 BC patients from western Algeria using ELISA technique, with optical density measured at a wavelength of 450 nm. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 expression were assessed by immunohistochemistry. Venous blood samples were collected in heparinized tubes. Additionally, stress and anxiety levels were evaluated using standardized questionnaires and compared with the other measured parameters. Results: Analysis of the correlations between the various variables revealed a positive correlation between anxiety and HIF-1α (p = 0.049, pearson correlation coefficient [PC] = 0.24), as well as between anxiety and the Scarff-Bloom-Richardson (SBR) grade (p = 0.037, PC = 0.26). A negative association was also observed between HIF-1α and HER2 status (p = 0.02, with the mean HIF-1α level in HER2-positive patients being 0.01 compared to 0.27 in HER2-negative patients). No significant association was found between IL-6 and stress (p = 0.4), nor between IL-6 and anxiety (p = 0.28). Conclusion: Our results show a positive correlation between anxiety and HIF-1α, which plays a crucial role in tumor angiogenesis, as well as with SBR grade. These findings suggest that anxiety may modulate tumor angiogenesis and contribute to increased tumor aggressiveness and grade. A negative association was also observed between HER2 and HIF-1α, which may be explained by a negative regulatory mechanism between the HER2 and HIF-1α signaling pathways. Furthermore, no association was found between stress or anxiety and IL-6 levels.

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